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1. WO2021037281 - THREE-DIMENSIONAL SPHERICAL ALPHA-HELIX CATIONIC POLYPEPTIDE HAVING HIGH-EFFICIENCY GENE DELIVERY CAPABILITY, AND PREPARATION METHOD AND APPLICATION THEREOF

Publication Number WO/2021/037281
Publication Date 04.03.2021
International Application No. PCT/CN2020/119113
International Filing Date 29.09.2020
IPC
C08G 69/48 2006.01
CCHEMISTRY; METALLURGY
08ORGANIC MACROMOLECULAR COMPOUNDS; THEIR PREPARATION OR CHEMICAL WORKING-UP; COMPOSITIONS BASED THEREON
GMACROMOLECULAR COMPOUNDS OBTAINED OTHERWISE THAN BY REACTIONS ONLY INVOLVING CARBON-TO-CARBON UNSATURATED BONDS
69Macromolecular compounds obtained by reactions forming a carboxylic amide link in the main chain of the macromolecule
48Polymers modified by chemical after-treatment
C08G 69/40 2006.01
CCHEMISTRY; METALLURGY
08ORGANIC MACROMOLECULAR COMPOUNDS; THEIR PREPARATION OR CHEMICAL WORKING-UP; COMPOSITIONS BASED THEREON
GMACROMOLECULAR COMPOUNDS OBTAINED OTHERWISE THAN BY REACTIONS ONLY INVOLVING CARBON-TO-CARBON UNSATURATED BONDS
69Macromolecular compounds obtained by reactions forming a carboxylic amide link in the main chain of the macromolecule
40Polyamides containing oxygen in the form of ether groups
C08G 69/32 2006.01
CCHEMISTRY; METALLURGY
08ORGANIC MACROMOLECULAR COMPOUNDS; THEIR PREPARATION OR CHEMICAL WORKING-UP; COMPOSITIONS BASED THEREON
GMACROMOLECULAR COMPOUNDS OBTAINED OTHERWISE THAN BY REACTIONS ONLY INVOLVING CARBON-TO-CARBON UNSATURATED BONDS
69Macromolecular compounds obtained by reactions forming a carboxylic amide link in the main chain of the macromolecule
02Polyamides derived from amino carboxylic acids or from polyamines and polycarboxylic acids
26derived from polyamines and polycarboxylic acids
32from aromatic diamines and aromatic dicarboxylic acids with both amino and carboxylic groups aromatically bound
A61K 47/42 2017.01
AHUMAN NECESSITIES
61MEDICAL OR VETERINARY SCIENCE; HYGIENE
KPREPARATIONS FOR MEDICAL, DENTAL, OR TOILET PURPOSES
47Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
30Macromolecular organic or inorganic compounds, e.g. inorganic polyphosphates
42Proteins; Polypeptides; Degradation products thereof; Derivatives thereof, e.g. albumin, gelatin or zein
A61K 9/14 2006.01
AHUMAN NECESSITIES
61MEDICAL OR VETERINARY SCIENCE; HYGIENE
KPREPARATIONS FOR MEDICAL, DENTAL, OR TOILET PURPOSES
9Medicinal preparations characterised by special physical form
14Particulate form, e.g. powders
A61P 35/00 2006.01
AHUMAN NECESSITIES
61MEDICAL OR VETERINARY SCIENCE; HYGIENE
PSPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
35Antineoplastic agents
CPC
A61K 47/42
AHUMAN NECESSITIES
61MEDICAL OR VETERINARY SCIENCE; HYGIENE
KPREPARATIONS FOR MEDICAL, DENTAL, OR TOILET PURPOSES
47Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
30Macromolecular organic or inorganic compounds, e.g. inorganic polyphosphates
42Proteins; Polypeptides; Degradation products thereof; Derivatives thereof, e.g. albumin, gelatin or zein
A61K 48/0008
AHUMAN NECESSITIES
61MEDICAL OR VETERINARY SCIENCE; HYGIENE
KPREPARATIONS FOR MEDICAL, DENTAL, OR TOILET PURPOSES
48Medicinal preparations containing genetic material which is inserted into cells of the living body to treat genetic diseases; Gene therapy
0008characterised by an aspect of the 'non-active' part of the composition delivered, e.g. wherein such 'non-active' part is not delivered simultaneously with the 'active' part of the composition
A61P 35/00
AHUMAN NECESSITIES
61MEDICAL OR VETERINARY SCIENCE; HYGIENE
PSPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
35Antineoplastic agents
C08G 69/16
CCHEMISTRY; METALLURGY
08ORGANIC MACROMOLECULAR COMPOUNDS; THEIR PREPARATION OR CHEMICAL WORKING-UP; COMPOSITIONS BASED THEREON
GMACROMOLECULAR COMPOUNDS OBTAINED OTHERWISE THAN BY REACTIONS ONLY INVOLVING UNSATURATED CARBON-TO-CARBON BONDS
69Macromolecular compounds obtained by reactions forming a carboxylic amide link in the main chain of the macromolecule
02Polyamides derived from amino-carboxylic acids or from polyamines and polycarboxylic acids
08derived from amino-carboxylic acids
14Lactams
16Preparatory processes
C08G 69/48
CCHEMISTRY; METALLURGY
08ORGANIC MACROMOLECULAR COMPOUNDS; THEIR PREPARATION OR CHEMICAL WORKING-UP; COMPOSITIONS BASED THEREON
GMACROMOLECULAR COMPOUNDS OBTAINED OTHERWISE THAN BY REACTIONS ONLY INVOLVING UNSATURATED CARBON-TO-CARBON BONDS
69Macromolecular compounds obtained by reactions forming a carboxylic amide link in the main chain of the macromolecule
48Polymers modified by chemical after-treatment
Applicants
  • 苏州大学 SOOCHOW UNIVERSITY [CN]/[CN]
Inventors
  • 殷黎晨 YIN, Lichen
  • 叶桓 YE, Huan
  • 党娟娟 DANG, Juanjuan
  • 侯梦滢 HOU, Mengying
  • 朱蓉英 ZHU, Rongying
Agents
  • 苏州创元专利商标事务所有限公司 SUZHOU CREATOR PATENT AND TRADEMARK AGENCY, LTD
Priority Data
201910817961.430.08.2019CN
Publication Language Chinese (ZH)
Filing Language Chinese (ZH)
Designated States
Title
(EN) THREE-DIMENSIONAL SPHERICAL ALPHA-HELIX CATIONIC POLYPEPTIDE HAVING HIGH-EFFICIENCY GENE DELIVERY CAPABILITY, AND PREPARATION METHOD AND APPLICATION THEREOF
(FR) POLYPEPTIDE CATIONIQUE D'HÉLICE ALPHA SPHÉRIQUE TRIDIMENSIONNELLE AYANT UNE CAPACITÉ D'INSERTION DE GÈNES À EFFICACITÉ ÉLEVÉE ET SON PROCÉDÉ DE PRÉPARATION ET APPLICATION ASSOCIÉE
(ZH) 具有高效基因递送能力的三维球形α螺旋阳离子聚多肽及其制备方法与应用
Abstract
(EN)
A three-dimensional star-shaped α-helix polypeptide having a high-efficiency gene delivery capability, and a preparation method and an application thereof. A dendrimer is used as an initiator and dichloromethane is used as a reaction solvent to initiate high-speed ring-opening polymerization of different types of N-carboxylic anhydride monomers, and groups having different electrical properties are introduced at the ends via click chemistry reactions. The abundant amino groups on the surface of the dendrimer provide enough polymerization sites to enable the polypeptide to form a three-dimensional spherical topological structure, and the topological structure provides an opportunity for initial acceleration of the ring-opening polymerization reaction. The higher positive charge density caused by polypeptide side chain modified guanidine/amino groups etc. achieves a high-efficiency gene loading capability by means of the electrostatic effect between positive and negative charges, and the α-helix rigid structure on the secondary structure thus enables the polypeptide to have a stronger membrane penetration capability.
(FR)
L'invention concerne un polypeptide d'hélice α en forme d'étoile tridimensionnelle ayant une capacité d'insertion de gènes à efficacité élevée et son procédé de préparation et une application associée. Un dendrimère est utilisé comme initiateur et du dichlorométhane est utilisé comme solvant de réaction pour initier la polymérisation par ouverture de cycle à vitesse élevée de différents types de monomères d'anhydrides N-carboxyliques, et des groupes ayant différentes propriétés électriques sont introduits aux extrémités par l'intermédiaire de réactions de chimie clic. Les groupes amino abondants sur la surface du dendrimère fournissent suffisamment de sites de polymérisation pour permettre au polypeptide de former une structure topologique sphérique tridimensionnelle, et la structure topologique fournit une opportunité d'accélération initiale de la réaction de polymérisation par ouverture de cycle. La densité de charge positive supérieure provoquée par les groupes guanidine/amino modifiés de chaîne latérale polypeptidique, etc., permet d'obtenir une capacité de chargement de gènes à efficacité élevée au moyen de l'effet électrostatique entre les charges positives et négatives, et la structure rigide d'hélice α sur la structure secondaire permet ainsi au polypeptide d'avoir une capacité de pénétration de membrane plus forte.
(ZH)
一种具有高效基因递送能力的三维星型α螺旋聚多肽及其制备方法与应用,以树枝状分子为引发剂,二氯甲烷为反应溶剂,引发不同类型的N-羧酸酐单体的高速开环聚合,并通过点击化学反应在末端引入不同电性的基团。树枝状分子表面丰富的氨基提供了足够的聚合位点,使聚多肽形成了三维球形拓扑结构,同时拓扑结构为开环聚合反应初期的加速作用提供了契机。聚多肽侧链修饰的胍基/氨基等带来了较高的正电荷密度,可以通过正负电荷间的静电作用获得高效的基因负载能力,且增强了二级结构上的α螺旋刚性结构进而使聚多肽拥有更强的穿膜能力。
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